Prostatic tumor cell plasticity involves cooperative interactions of distinct phenotypic subpopulations: role in vasculogenic mimicry.

Background: Tumor cell plasticity represents a significant clinical challenge in that the fate and function of tumor cells can be elusive until a tumor mass is evident. A remarkable example of plasticity is tumor cell vasculogenic mimicry, recently described in aggressive uveal and cutaneous melanoma, in addition to ovarian carcinoma, whereby tumor cells express endothelial-associated genes and form de novo vasculogenic-like networks in three-dimensional (3-D) culture. In the current investigation, we examined whether there is evidence for vasculogenic mimicry in heterogeneous prostatic neoplasms.

Methods: Dunning rat and human prostate cancer cell lines (comprised of epithelial- and fibroblastic-like tumor subpopulations) were tested for their ability to express selected endothelial-associated genes, laminin, the alpha6beta1 laminin-binding integrin, and for their potential to form perfusable tubular networks in 3-D culture. Simultaneous morphological analysis of tumor-lined channels in rat and human tumors was also performed.

Results: Green fluorescent protein labeling of prostatic clonal subpopulations revealed unique cooperative interactions of epithelial- and fibroblastic-like tumor cells in the formation of perfusable vasculogenic-like networks. Furthermore, while these cell lines were shown to express various vascular markers, prostatic tumor cell-lined channels were also detected in vivo in high grade tumors, and occurred in some cases in close proximity to conventional endothelial-lined vasculature.

Conclusions: A multidisciplinary approach to assess vasculogenic mimicry by prostatic tumor cells has revealed supportive evidence that it occurs in invasive, heterogeneous prostate cancer cell lines, and circumstantially in aggressive rat and human tumors. These results reflect the plasticity of aggressive prostatic tumor cells and may provide new prognostic markers for clinical diagnosis and new therapeutic intervention strategies.